The chief objective of this investigation is to clarify the mechanism of action of cardiac cytochrome oxidase. The interrelationships of cytochromes a and a3 and copper in the enzyme will be studied in heart muscle using spectrophotometric and electron paramagnetic resonance (EPR) techniques. An oxidase preparation depleted of EPR-visible copper or of total copper will be used in these studies. A cytochrome oxidase from Pseudomonas aeruginosa will be studied as a model for the cardiac enzyme. Research will include crystal structure, modification of heme groups, amino acid sequence, and kinetics of oxygen reduction. The purpose of these investigations is to help understand the bioenergetic processes of heart muscle in health and disease.